Analysis of a polycytosine tract and heteroplasmic length variation in the mitochondrial DNA D-loop of patients with diabetes, MELAS syndrome and race-matched controls
Analysis of a polycytosine tract and heteroplasmic length variation in the mitochondrial DNA D-loop of patients with diabetes, MELAS syndrome and race-matched controls
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DOI：
10.1046/j.1464-5491.2001.00477.x
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发表时间：
2001-05-01
影响因子：
3.5
通讯作者：
Alcolado, JC
中科院分区：
文献类型：
--
作者：
Gill-Randall, R;Sherratt, EJ;Alcolado, JC
目的研究人线粒体基因组16189位碱基T → C置换与线粒体DNA控制区异质性长度变异的关系。以前的报道表明，这种缺陷可能与其他致病性mtDNA突变的发生有关，包括tRNA中的致糖尿病性A至G突变（LEU（UUR））。最近，16189 nt变异也与英国成年男性的胰岛素抵抗有关。为了进一步研究这些相关性，我们研究了23名3243 nt突变的患者，方法采用聚合酶链反应（PCR）技术检测16189 nt附近区域的DNA片段，并与150例2型糖尿病患者和149例非糖尿病对照者进行比较。结果我们发现16189 nt处T → C的替换与T-DNA多态性有关，只有当所得到的多胞嘧啶序列不被第二次突变中断时，才存在异质性长度变异。3243 nt突变的患者，2型糖尿病患者或种族匹配的正常controls. Conclusions之间的16189 nt变异或异质体长度变异的患病率没有显着差异，包括这些变异可能代表正常的多态性和以前报道的协会应谨慎对待，除非它们可以在其他人群中复制。
Aim The T to C substitution at position 16189 nt of the human mitochondrial genome has been associated with the development of heteroplasmic length variation in the control region of mtDNA. Previous reports have suggested that this defect may be associated with the development of other pathogenic mtDNA mutations, including the diabetogenic A to G mutation in the tRNA(LEU(UUR)). Recently the 16189 nt variant has also been associated with insulin resistance in British adult men. In order to investigate these associations further we studied 23 patients with the 3243 nt mutation, 150 patients with Type 2 diabetes and 149 non-diabetic controls.Methods The region around 16189 nt was investigated by polymerase chain reaction-restriction fragment length polymorphism analysis and automated sequencing.Results We find that the T to C substitution at 16189 nt is associated with heteroplasmic length variation only when the resultant polycytosine tract is not interrupted by a second mutation. There are no significant differences in the prevalence of the 16189 nt variant or heteroplasmic length variation between patients with the 3243 nt mutation, patients with Type 2 diabetes or race-matched normal controls.Conclusions include that these variants are likely to represent normal polymorphisms and that previously reported associations should be treated with caution unless they can be replicated in other populations.